Progress in technology has resulted in the release into the environment of many chemical substances which subsequently have been shown to exhibit mutagenic, carcinogenic, teratogenic or toxic properties. Many of these substances exhibit little if any of these pharmacologic activities unless metabolically activated within the target system. The heme protein, cytochrome P448 plays a vital role as part of the microsomal oxygenase system which catalyzes this activation. It is known that the cytochrome P448 complex is inducible upon exposure of animals to a wide variety of environmental pollutants, including the Arochlors and 3-methylcholanthrene (3MC). Our previous work has suggested that the effect of at least 3MC is mediated at both the levels of transcription and translation. The present study is aimed at: a) definitively establishing an increase in the hepatic level of the messenger RNA for cytochrome P448 after administration of Arochlor 1254 or 3MC to rats, b) determining the number of copies of cytochrome P448 messenger RNA transcribed in vivo before and after administration of 3MC or Arochlor 1254 to rats, c) determining the gene dosage for this messenger RNA in fetal and adult rat liver and d) quantifying the cytochrome P448 messenger RNA sequences during normal liver development. Toward these ends, liver messenger RNA fractions will be isolated from drug-treated rats by Sepharose 4B and poly U-Sepharose chromatography and will be tested for translational activity in a wheat germ translational system. The products of the wheat germ translational system will be examined by SDS-gel electrophoresis and will be immunoprecipitated with antibody produced to cytochrome P448. Purified cytochrome P448 mRNA will be used to produce cDNA by the AMV reverse transcriptase reaction and the cDNA will then be employed in hybridization assays to ascertain gene dosage, and ontogenetic expression of cytochrome P448 mRNA. These studies will supply some important information about the transcription of a most important component of a system which is absolutely necessary, not only for detoxification, but for activation of promutagens, proteratogens, and procarcinogens.